Israel Institute for Biological Research (IIBR) expect to begin human trials for the COVID-19 vaccine

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Israeli researchers from the government-run Israel Institute for Biological Research (IIBR) expect to begin human trials for the COVID-19 vaccine candidate they developed after the high holidays this fall.

“The Institute for Biological Research in Ness Ziona has been preparing for years for an event such as an outbreak from the COVID-19 family,” Bennett wrote.

“The institute’s scientists worked arduously for 24 hours a day and managed to develop a vaccine and register a patent on it.

The vaccine worked excellently in the lab, and excellently in animal trials.

Prime Minister Benjamin Netanyahu spoke with IIBR Director-General Professor Shmuel C. Shapira on Thursday, as well as with heads of the IIBR research team and “congratulated them on the progress in developing a vaccine against the coronavirus, ahead of the stage of human trials, which will start after the fall holidays,” the Government Press Office said in a statement.

“I am pleased to hear about the progress and I want to congratulate you on it. Continue on this path with the maximum speed that you deem scientifically sufficient,” Netanyahu said, according to the announcement.

Defense Minister and Alternate Prime Minister Benny Gantz visited the Ness Ziona-based research institute on Thursday, the Jerusalem Post reported.

PM Benjamin Netanyahu speaks with IIBR Director General Prof. Shmuel Shapira via viodeconference. Photo: Kobi Gideon
PM Benjamin Netanyahu speaks with IIBR Director General Prof. Shmuel Shapira via viodeconference. Photo: Kobi Gideon

“Experiments on humans should begin after the Tishrei holidays,” Gantz was quoted as saying in reference to the first month of the Hebrew calendar when the high holidays begin.

“The human trials will be conducted in collaboration with the Health Ministry…and according to all the processes required in terms of medical safety,” Gantz added.

Professor Shapira said the institute developed “an excellent vaccine” over the past six months. During the call with Netanyahu, he held up a vial and said: “This is the first vial of the vaccine.”

Netanyahu instructed that evaluations begin on the establishment of vaccine production in Israel “so that Israel will have safe and effective vaccines for all residents of Israel by the end of the first quarter of 2021.”

He also instructed that an outline be drawn up to allow other countries to purchase vaccine options from Israel.

“The financing thus obtained will be able to assist in the establishment of production capabilities and processes,” he said, according to the announcement.

The Israeli delegation collected 20,000 samples from COVID-19 patients in India. Photo: Defense Ministry
An Israeli delegation of researchers collected 20,000 samples from COVID-19 patients in India in July-August 2020. Photo: Defense Ministry

The premier tapped the IIBR, a governmental research center specializing in biology, chemistry and environmental sciences that falls under the jurisdiction of the Prime Minister’s Office, in early February to begin development on producing a vaccine.

The institute has announced several developments since then. In June, researchers indicated that a vaccine they developed for SARS CoV-2, the virus that causes COVID-19, was found to be effective in trials involving hamsters, paving the way for testing with humans.

Previously, the center reported “significant progress” on the vaccine and initial trials.

The secretive institute has also been working on researching potential treatments and in early May announced that it made a breakthrough on a treatment involving a discovered antibody that neutralizes the virus.

That same month, it further announced that researchers found that a combination of two existing antiviral drugs for Gaucher disease appears to inhibit the growth of SARS CoV-2, and may work against other viral infections, including a common flu strain.

Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID
Colorized scanning electron micrograph of an apoptotic cell (green) heavily infected with SARS-COV-2 virus particles (purple), isolated from a patient sample. Image captured and color-enhanced at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID CC BY 2.0, Flickr

According to the June announcement, the scientists indicated that the vaccine candidate they designed used vesicular stomatitis virus (VSV), an animal virus that does not cause disease in humans, and in which the spike protein was replaced with that of SARS-CoV-2. VSV is also the basis for a separate, effective vaccine against the Ebola virus.

The vaccine, which they called recombinant VSV-ΔG-spike or rVSV-ΔG-spike, was tested on golden Syrian hamsters and was shown to be “safe, well-tolerated, elicits antibodies, [is] able to bind and neutralize SARSCoV-2 efficiently,” according to the study.

How does it work ?

The researchers generated a replication competent recombinant VSV-ΔG-spike vaccine, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2. In vitro characterization of the recombinant VSV-ΔG-spike indicated expression and presentation of the spike protein on the viral membrane with antigenic similarity to SARS-CoV-2.

A golden Syrian hamster in vivo model for COVID-19 was implemented. We show that vaccination of hamsters with recombinant VSV-ΔG-spike results in rapid and potent induction of neutralizing antibodies against SARS-CoV-2.

Importantly, single-dose vaccination was able to protect hamsters against SARS-CoV-2 challenge, as demonstrated by the abrogation of body weight loss of the immunized hamsters compared to unvaccinated hamsters.

Furthermore, whereas lungs of infected hamsters displayed extensive tissue damage and high viral titers, immunized hamsters’ lungs showed only minor lung pathology, and no viral load. Taken together, we suggest recombinant VSV-ΔG-spike as a safe, efficacious and protective vaccine against SARS-CoV-2 infection.

The race for a coronavirus treatment or vaccine

Close to 200 teams worldwide are working to develop a vaccine or a treatment for COVID-19. Twenty-five are currently under clinical evaluation.

These include a promising vaccine candidate developed by Massachusetts-based company Moderna, which is currently in Phase III trials.

Another promising vaccine candidate, also in Phase III trials, was developed by the University of Oxford which recently signed a distribution agreement with drugmaker AstraZeneca.

Scientists at the Migal Galilee Research Institute scientists. Courtesy
Scientists at the Migal Galilee Research Institute scientists. Courtesy

In late April, Israeli scientists at the Migal Galilee Research Institute formed a new company, MigVax, to further adapt a vaccine they developed for a deadly coronavirus affecting poultry for human use.

The scientists had been working for four years to develop a vaccine for IBV (Infectious Bronchitis Virus) which affects the respiratory tract, gut, kidney and reproductive systems of domestic fowl. 

MigVax raised $12 million in an investment round led by OurCrowd for further development of the vaccine. The startup hopes to begin clinical trials this summer.

The MigVax approach utilizes a chimeric protein that presents the viral proteins to the immune system via the oropharynx.

This method, based on the IBV vaccine, generates three kinds of immunological response:

  1. mucosal immunity- IgA
  2. Blood-based immunity-IgG
  3. Cell-mediated immunity.

The MigVax vaccine is based on a vaccine developed for Infectious Bronchitis Virus which is a coronavirus that infects chickens.​

MigVax’s Vaccine

  • The MigVax vaccine is based on a vaccine developed for Infectious Bronchitis Virus which is a coronavirus that infects chickens. The vaccine was developed over the past 4 years in an attempt to immunize chickens and prevent the jump to humans (bird flu). The vaccine was successfully tested in chickens and not only was able to demonstrate neutralizing antibodies and cell-mediated immunity but more importantly, the vaccine prevented infection in immunized chickens from IBV challenge. To the best of our knowledge, this is the first vaccine to demonstrate prevention of challenge in an in-vivo setting.
  • ​Based on comparison of the IBV and COVID-19 it was seen that the basis of the chicken vaccine could provide a significant basis for the generation of a human vaccine
  • The MigVax approach utilizes a chimeric protein that presents the viral proteins to the immune system via the oropharynx. This approach (again based on the IBV vaccine) generates three kinds of immunological response: 1. mucosal immunity- IgA 2. Blood-based immunity-IgG 3. Cell mediated immunity.
  • Mucosal immunity can prevent infection via the oropharynx. This is significant because it has the chance to prevent a detrimental immune response that may result with only IgG based immunity. Cell mediated immunity, may help clear viral infected cells.
  • On the manufacturing side, the vaccine is made using bacterial fermentation, thus the ability to manufacture millions of doses quickly is easily attainable.​
  • Based on actual in vivo efficacy in preventing infection, oral based vaccine and three pronged immunity gives the MigVax approach a unique standing among the other approaches. In addition to significant advantages in manufacturing and cost.
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The Main Achievements of the Program

A proof-of-concept was achieved using an Avian coronavirus sequence for vaccination of chickens against the Avian Infectious Bronchitis (IBV) virus.

  • Definition of specific structural motifs of the corona S and N proteins, sufficient for induction of effective immune response.
  • Development of three chimeric proteins for carrying three distinct structural domains, with enhanced mucosal activity for mucosal vaccination.
  • Development of an E. coli-based protein expression system that produces and secretes the chimeric proteins to the growth media.
  • Proof-of-concept for safety, specific antibody induction, activation of the cellular immune response, and protection against the challenge, was performed in two medium-scale animal studies, in chicken models and Avian corona H120 IBV.
  • Development of fermentation media and process for protein production, following pharma regulations and GMP standards.    

Advantages of the MigVax Vaccine

  • Platform technology: MigVax claims its human vaccine development, based on the development of the avian corona virus IBV vaccine, is a generic system for developing subunit corona virus vaccines. The system includes 3 protein elements (one S and two Ns) fused with an adjuvant carrier protein.
  • Ease of switching: The basis of the current MigVax vaccine is built upon the ability to take avian corona virus proteins and convert them to human corona proteins, making it a viable platform for vaccine development with the ability to adapt against the high rate of COVID-19 virus mutation.[1] This rapid switch to newer mutated proteins is an important advantage compared to other technologies.
  • Oral administration: This has a 2-fold effect. Firstly, the ease of administration, especially essential in mass vaccination; and secondly, the mucosal immunity at the site of administration and site of natural virus port of entry – oral mucosa, tonsils, adenoids.
  • Triple-arm immunity: As mentioned above, the MigVax approach is believed to have three kinds of immunal response: mucosal, through site of administration; humoral, through neutralizing antibodies to S protein; and cellular, induced by N proteins component of the vaccine (mucosal IgA, IgG and T-cell response).
  • Safety: no live viral particles; triple-arm immunity may defend from antibody-dependent enhancement
  • Efficient and cost-effective large-scale manufacturing: This is critical in the case of mass vaccination and may be the limiting factor for other technologies; traditional and confirmed technologies, no risk involved (as opposed to newer technologies).​

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